Parts of the area surrounding the river, including both the Blue Mountains National Park and the Wollemi National Park have received World Heritage listing, due in part to the discovery of the Wollemi Pine, often described as a 'living fossil' from the age of the dinosaurs. The Colo River gorge contains many boulder-rapids that alternate with deep pools. Even though this area is relatively close to the Sydney metropolitan area, the Colo River flows through the largest wilderness area in New South Wales. Local volunteer bush regeneration groups such as the "Friends of the Colo" have been helping eradicate invasive exotic weeds in the area surrounding the river.[citation needed]

The area of the lower Colo River was first explored by Europeans in June 1789 by Governor Philiip and settlement commenced from the early 1800s via land grants, that were significantly expanded from 1833. The Colo River was an important transport corridor in the period before motor vehicles, with produce and goods transported down the Hawkesbury River to Sydney.[4]